PS1
Not met: no pathogenic record of p.Gly1501Arg via a different nucleotide change exists; ClinVar classifies this variant as Uncertain significance.
PS2
Not assessed: no de novo occurrence of this variant in a tested proband is documented in any source.
PS3
Not assessed: no variant-specific functional study of p.Gly1501Arg exists; OncoKB reports no functional evidence.
PS4
Not met: the variant is absent from the Leon-Castillo recurrent-variant table and COSMIC, failing the somatic-recurrence rule.
PM1
Not met: residue 1501 lies outside the exonuclease proofreading domain (residues 286-459) containing all established hotspots.
PM3
Not assessed: no proband genotyping or phase data exist to test for a variant in trans with a pathogenic allele.
PM5
Not assessed: no pathogenic comparator at residue 1501 was found, though its absence is not comprehensively confirmed.
PM6
Not assessed: no de novo occurrence is documented with or without parentage confirmation.
PP1
Not assessed: no segregation or family-testing data document any informative meiosis.
PP2
Not assessed: no gene-level missense constraint data (e.g., gnomAD Z-score) are available to evaluate this rule.
PP3
Not met: REVEL 0.492 falls below the supporting threshold of 0.644, and SpliceAI max delta 0.01 shows no splice impact.
PP4
Not assessed: no phenotype or family-history data for any carrier are available.
PP5
Not met: ClinVar classifies this variant as Uncertain significance with no expert-panel submission.
